The causative agent of the acquired immune deficiency syndrome (AIDS), an inevitably fatal disease, appears to be a member of a closely related family of RNA viruses, called human T-lymphotropic virus type III (HTLV-III) or lymphadenopathy-associated virus (LAV). The host range of this virus is defined by cells which bear the surface glycoprotein T4. Indeed, all available evidence indicates that T4 is the membrane-anchored receptor for HTLV-III/LAV. Clinical studies suggest that the progression of disease can be correlated with depletion of a functional class of immune system regulatory cells, T-helper lymphocytes, which display the T4 surface protein and that this T-cell depletion, with ensuing immunological compromise, might result from recurrent cycles of infection and lytic growth. This suggests a therapeutic strategy for the treatment of AIDS and pre-AIDS. We propose that recombinant soluble T4 protein will serve to sequester free HTLV-III/LAV by acting as soluble virus receptor, and that this will retard or completely inhibit virus growth in infected individuals. The steps toward producing recombinant soluble T4 and testing its potential as a therapy in the treatment of AIDS are straightforward, and they are outlined in this proposal.